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Evaluating a pragmatic estimate of insulin sensitivity in Latino youth with obesity.

ABSTRACT: The whole-body insulin sensitivity index (WBISI) is a widely used surrogate of insulin sensitivity estimated from glucose and insulin concentrations during an oral glucose tolerance test (OGTT). The original WBISI uses five timepoints but reduced sampling models have been proposed. These reduced models have not been applied to the paediatric population. The purpose of this study is to compare cross-sectional agreement and changes in response to lifestyle intervention between the original WBISI and the WBISI₁₂₀ using fasting and 2-hour glucose and insulin concentrations from OGTT among Latino adolescents with obesity. We also examined the cost-differential between the two measures. Secondary analyses were conducted with data from Latino adolescents (14-16 years) with obesity (BMI ≥ 95th percentile) who were recruited for a randomized controlled lifestyle intervention trial. Baseline data in youth (n = 148) who underwent a 2-hour OGTT was used to analyse agreement between WBISI and WBISI₁₂₀ . Data from 65 participants who completed a 12-week lifestyle intervention were used to assess changes and the rate of change between WBISI and WBISI₁₂₀ . Research costs to determine both measures were compared. WBISI₁₂₀ showed good cross-sectional agreement (ICC_agreement = 0.88) with the full WBISI. Following intervention, WBISI₁₂₀ increased 62.5% (M ± SD, 1.6 ± 1.2 to 2.6 ± 1.7, P < .001) while WBISI increased by 25.0% (1.6 ± 1.0 to 2.0 ± 1.0, P < .001) but the rate of change for WBISI and WBISI₁₂₀ was not significantly different (P = .11). WBISI₁₂₀ costs ~70% less than WBISI. WBISI₁₂₀ may offer a cost-effective surrogate estimate of insulin sensitivity in Latino youth with obesity.

SUBMITTER: Pena A

PROVIDER: S-EPMC9275660 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ContextYouth with obesity and abnormal glucose tolerance have an increased risk for atherosclerosis but the relative contributions of insulin resistance and hyperglycemia to dyslipidemia and the development of subclinical atherosclerosis are unknown.ObjectiveThis work aims to determine the association between insulin resistance, dyslipidemia, and carotid intimal thickness (cIMT) in adolescents with normal and abnormal glucose tolerance.MethodsAn observational cohort study in 155 youth: 44 obese insulin sensitive (OIS; fasting insulin ≤ 20 µM/mL, body mass index [BMI] ≥ 95th percentile), 35 obese insulin resistant (OIR; fasting insulin > 20 µM/mL, BMI ≥ 95th percentile), 34 obese abnormal glucose tolerant (AGT; BMI ≥ 95th percentile), and 42 Lean (BMI 5th-85th percentile). Lipids, lipoprotein particle size and concentration (-P), insulin sensitivity (SI an intravenous glucose test), and CMIT were compared using linear models adjusted for age, race/ethnicity, biological sex, and Tanner stage. Lipid/lipoprotein profile and CMIT were reevaluated in a subset after 2 years.ResultsCompared to OIS and Lean, OIR and AGT had elevated triglycerides and low high-density lipoprotein cholesterol (HDL-C) but similar total cholesterol and low-density lipoprotein cholesterol (LDL-C). Among OIS, OIR, AGT, lower SI was associated with atherogenic lipids (higher triglycerides, LDL-C, non-HDL-C, and lower HDL-C) and lipoproteins (higher total LDL-P and small HDL-P, and lower large HDL-P). There was a steeper decline in the association of SI with HDL-C and large HDL-P in AGT compared with OIR and OIS. cIMT was comparable across groups and inversely correlated with SI, with no change after 2 years.ConclusionAmong youth with obesity, insulin resistance was associated with an atherogenic lipoprotein/lipid profile and cIMT, regardless of glucose tolerance status. Insulin resistance in AGT youth was associated with a shift to smaller HDL-P compared to normoglycemic youth with obesity. Alterations in HDL-P metabolism may be early adverse manifestations of hyperglycemia in youth with obesity.

Project description:BACKGROUND:Obesity and pubertal insulin resistance worsen cardiovascular (CV) risk factors in youth. It is unclear how the relationships of obesity and insulin resistance with CV risk compare to adults. SUBJECTS AND METHODS:We evaluated 66 pubertal youth (mean?±?SD: age 14.2 ± 2.0?years, body mass index [BMI] 36.6 ± 6.0 kg/m2 , hemoglobin A1c [HbA1c] 38.5 ± 6.1 mmol/mol) and 355 adults with comparable BMI (age 52.7 ± 9.4?years, BMI 35.1 ± 5.1 kg/m2 , HbA1c 39.8 ± 4.2 mmol/mol) participating in a multicenter study. Insulin sensitivity was quantified using hyperglycemic clamps. Assessment of CV risk factors was standardized across sites. Regression analyses compared the impact of insulin sensitivity and CV risk factors between youth and adults. RESULTS:Obese pubertal youth were more insulin resistant than comparably obese adults (P <?.001), but with similar slopes for the inverse relationship between insulin sensitivity and obesity. The impact of obesity on CV risk factors was explained by insulin sensitivity (P =?NS after adjustment for sensitivity). The two age groups did not differ in relationships between insulin sensitivity and diastolic blood pressure, total cholesterol, and low-density lipoprotein (LDL) cholesterol, after adjusting for obesity. However, while systolic blood pressure (SBP) and high-density lipoprotein (HDL) cholesterol exhibited the expected direct and inverse relationships, respectively with insulin sensitivity in adults, these slopes were flat in youth across the range of insulin sensitivity (P ??.05 for group differences). CONCLUSIONS:Effects of obesity on CV risk factors were attributable to insulin sensitivity in both groups. The relationships between insulin sensitivity and CV risk factors were similar in obese youth and adult groups except for SBP and HDL cholesterol. CLINICAL TRIAL REGISTRATION:The RISE consortium studies are registered through Clinicaltrials.gov as NCT01779362 (Adult Medication Study); NCT01763346 (Adult Surgery Study); and NCT01779375 (Pediatric Medication Study). Clinical trial registration numbers: NCT01779362, NCT01779375 and NCT01763346 at clinicaltrials.gov.

Project description:Lifestyle intervention can improve insulin sensitivity in obese youth yet few studies have examined the biological mechanisms underlying improvements. Therefore, the purpose of this study was to explore biological pathways associated with intervention-induced improvements in insulin sensitivity. Fifteen (7M/8F) overweight/obese (BMI percentile=96.3M-BM-11.1) Latino adolescents (15.0M-BM-10.9 years) completed a 12-week lifestyle intervention that included weekly nutrition education and 180 minutes of moderate-vigorous exercise per week. Insulin sensitivity, estimated by an oral glucose tolerance test and the Matsuda Index, increased 29.2% post intervention (2.4M-BM-10.3 to 3.1M-BM-10.3, p=0.01). Global microarray analysis profiling from whole blood was performed to examine changes in gene expression and to explore biological pathways that were significantly changed in response to the intervention. A total of 1,459 probes corresponding to mRNA transcripts (717 up, 742 down) were differentially expressed with a fold changeM-bM-^IM-%1.2 and P<0.05. Among the genes identified were hexokinase 3 (HK3), ATPase, H+ transporting V0 subunit e2 (ATPV0E), and sterol regulatory element binding transcription factor 1 (SREBF1), and endothelial cell adhesion molecule (ESAM). There were 8 pathways identified that met the criteria for significance, including insulin signaling, type 1 diabetes, and glycerophospholipid metabolism. Participants that increased insulin sensitivity exhibited five times the number of significant genes altered compared to non-responders (1,144 vs. 230). These findings offer insight into the molecular mechanisms underlying health improvements among high-risk Latino youth. Lifestyle interventions may contribute to improved insulin sensitivity through pathways related to insulin signaling and immune response. Further, genetic factors may mediate response to lifestyle intervention. Fifteen (7M/8F) overweight/obese Latino Youth Whole blood RNA samples evaluated pre and post intervention.

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Evaluating a pragmatic estimate of insulin sensitivity in Latino youth with obesity.

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